The invention relates to a novel process for the synthesis of cinnamic esters or substituted cinnamic esters by condensation of carboxylic esters with benzaldehyde or substituted benzaldehydes, respectively, in the presence of a solid with basic properties.
Cinnamic esters and substituted cinnamic esters are used, for example, as light protection filters in cosmetic applications and in plastics. 2-Ethylhexyl 4-methoxycinnamate is a light protection filter for the wavelength range of light from 280-315 nm (UV-B), which is known inter alia under the names NeoHeliopan(copyright) AV and OMC (Ullmanns Encyclopedia of Industrial Chemistry 6th Edition, Electronic Release, 1999, Vol. A 24, 231-239).
The synthesis of cinnamic esters or of 2-ethylhexyl 4-methoxycinnamate has hitherto been described in the following ways:
A) Condensation of benzaldehyde with acetic ester in the presence of alkali metal alkoxide (Ullmanns Encyclopedia of Industrial Chemistry 6th Edition, Electronic Release, 1999, Vol. A 24, 231-239).
B) Coupling of 4-halogenoanisol with acrylic ester catalyzed by palladium salts in the presence of suitable bases and phosphine ligands (Ullmanns Encyclopedia of Industrial Chemistry 5th Edition, 1986, Vol. A 7, 99-101, WO 90/10617, EP A 056491 and EP A 0719758).
C) Coupling of 4-methoxydiazonium salts with acrylic ester catalyzed by palladium in the presence of suitable bases (Genxc3xaat; Tetrahydron Letters 1999, 4815).
D) Addition of ketene onto acetals of benzaldehyde or substituted benzaldehydes (EP A 0490198).
A disadvantage of said processes is either the large amount of undesired salts which form during the synthesis, the use of noble metal catalysts, which are expensive and usually difficult to recover, and the use of toxic starting materials or laborious preliminary stages or subsequent steps.
An object of the present invention is a process for the synthesis of substituted cinnamic esters in which, in one reaction step, using suitable catalysts, benzaldehyde or substituted benzaldehydes are linked with acetic esters in a condensation reaction.
We have found a process for the preparation of cinnamic esters or substituted cinnamic esters of the general formula (I) 
in which
R1, R2 and R3 are identical or different and are hydrogen, alkoxy or alkyl, and
R4 is alkyl,
which is characterized in that benzaldehydes (II) of the formula 
wherein
R1, R2, R3 have the meanings given above,
are reacted with carboxylic esters (III) 
where
R4 has the meaning given above
in the presence of a solid with basic properties.
Surprisingly, the cinnamic esters can be prepared by the process according to the present invention in one step without salt contamination. In the general formulae I, II and III, the following general meanings apply: alkyl is a straight-chain or branched hydrocarbon radical having 1 to 16, preferably 1-10, carbon atoms, such as, for example, ethyl, methyl, propyl, iso-propyl, butyl, pentyl, hexyl, heptyl, octyl, 2-ethylhexyl, nonyl and decyl.
Alkoxy is a straight-chain or branched hydrocarbon radical, bonded via oxygen, having 1 to 6, preferably 1 to 3, carbon atoms, such as, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentoxy, isopentoxy, hexoxy or isohexoxy.
Examples of benzaldehydes which may be mentioned are: 4-methoxybenzaldehyde, 4-ethoxybenzaldehyde, 4-propoxybenzaldehyde, 4-iso-propoxybenzaldehyde, 4-butoxybenzaldehyde, 4-pentoxybenzaldehyde, 4-iso-pentoxybenzaldehyde, 4-methylbenzaldehyde, 4-ethylbenzaldehyde, 4-iso-propylbenzaldehyde, 4-propylbenzaldehyde, 4-butylbenzaldehyde.
Examples of carboxylic esters which may be mentioned are: hexyl acetate, heptyl acetate, octyl acetate, 2-ethylhexyl acetate, nonyl acetate, decyl acetate.
A preferred benzaldehyde (II) is 4-methoxybenzaldehyde, and a preferred carboxylic ester is 2-ethylhexyl acetate.
The molar ratio of benzaldehyde to carboxylic ester is generally in the range from 0.01 to 10, preferably in the range from 0.1 to 1 and most preferably, in the range from 0.2 to 0.5.
The process according to the present invention can be carried out in solvents or without diluent.
Solvents for the process according to the present invention are, for example, toluene, xylene, chlorobenzene, dichlorobenzene.
Water, which forms during the reaction is preferably removed according to the present invention from the reaction mixture, more preferably by distillation.
Entrainers for the water of reaction during the distillation which may be used are the solvents used or the carboxylic ester (III). The water can be separated off in a separator, it being possible to place the separator directly on the reactor or to use a separating column between reactor and separator. Water removal from the system is possible during reflux of the reaction solution or of the solvent.
Basic solids used for the process according to the present invention are metal carbonates and metal oxides, mixed oxides, mixtures of metal carbonates, mixtures of metal oxides and mixtures of metal carbonates and metal oxides. Preference is given to alkali metal and alkaline earth metal carbonates and oxides and, of these, the carbonates and oxides of sodium, caesium, potassium, magnesium and calcium. Aluminum oxide, zinc oxide and zirconium oxide may also be mentioned as basic solids.
A most preferred embodiment is potassium carbonate and caesium carbonate.
The basic solids can also be doped by sodium oxide, potassium fluoride, cerium oxide, ammonium fluoride, potassium carbonate and caesium carbonate.
The doping is preferably added in an amount of from 0.1 to 50% by weight, preferably in an amount of from 5 to 50% by weight, based on the total amount of the basic solid.
The solids can be used in pure form, supported or as a mixture, preference being given to mixtures of potassium carbonate and caesium carbonate, and more preference given to mixtures of caesium carbonate and potassium carbonate in which the two carbonates are used in equal parts by mass. The catalyst concentrations can be between 0.1 and 50% (w/w), preferred catalyst concentrations are between 5 and 50% (w/w). The catalyst can be thermally or mechanically pretreated prior to the reaction and can be used in powder form or as moldings.
Basic insoluble solids, specifically inorganic, basic, insoluble solids, are known per se as catalysts for condensation reactions of the aldol type (Chem. Rev., 1995, 95, 537-558, Catal. Today, 1997, 38, 321-337), where carbonyl compounds, such as aldehydes and ketones, are reacted with Cxe2x80x94H-acidic compounds. A disadvantage of the described processes is the limitation to Cxe2x80x94H-acidic compounds with Cxe2x80x94H acidities which have an approximate pKa value (Advanced Organic Chemistry, J. March, 3rd Edition, 1985, 220-221) of less than 20. Processes for the preparation of cinnamic esters or substituted cinnamic esters by reacting acetic esters as Cxe2x80x94H-acidic compound with benzaldehyde or substituted benzaldehydes are not described.
Inorganic solids, specifically oxides, with halogen-containing compounds, modified oxides, carbonates, mixtures of carbonates, mixtures of carbonates and oxides, characterized in that the substances have basic properties, are suitable catalysts for the synthesis of cinnamic esters or substituted cinnamic esters from benzaldehyde or substituted benzaldehydes, respectively, and acetic esters. This is surprising since inorganic solids are attributed with having a significantly lower basicity than, for example, alkali metal alkoxides, which are used in condensation reactions of the type described. The high activity and selectivity which is achieved with potassium carbonate and caesium carbonate in said reaction was particularly surprising. Moreover, an unexpected synergistic effect of potassium carbonate and caesium carbonate is found, i.e. the activity of the physical mixture of the two carbonates produces higher activities than the activities of the pure substances suggest.
The reaction pressure can be in the range from 0.1 to 10 bar, preferably in the range from 0.5 to 2 bar.
The reaction temperature is generally in the range from 100xc2x0 C. to 300xc2x0 C., preferably 150xc2x0 C. to 250xc2x0 C.
The reaction time can be between 0.5 and 48 h; preferred reaction times are between 0.5 and 5 h.
The reaction mixture must be thoroughly mixed during the reaction, which can take place by the boiling reaction solution alone and by the additional use of a stirrer. Isolation of the reaction product is carried out following removal of the catalyst by distillation under reduced pressure. The catalyst can be separated off by filtration and, in cases where the catalyst is water-soluble, by the addition of water, dissolution of the catalyst solid and subsequent phase separation.
The process according to the present invention can be represented by the following equation: 
The process according to the present invention can be carried out, for example, as follows:
In general, 5-20% (w/w) of catalyst, which is either used without further pretreatment or prior to the reaction has been heated at elevated temperature or ground, are taken up in, for example, 2-ethylhexyl acetate and the reaction mixture is heated to the reflux temperature, then 4-methoxybenzaldehyde is added, the molar ratio of aldehyde to carboxylic ester being between 0.1 and 1. The progress of the reaction is ascertained by means of the water of reaction which forms and also by means of sampling and gas chromatographic analysis of the samples. When the reaction is complete, the catalyst is filtered off and the filtrate is distilled at subatmospheric pressure.
Using the present inventions it is possible to prepare cinnamic esters or substituted cinnamic esters by condensation of carboxylic esters with benzaldehyde or substituted benzaldehydes, respectively, catalyzed by a solid with basic properties with continuous removal of the water of reaction which forms.
Preferably, 2-ethylhexyl 4-methoxycinnamate can be prepared by the process according to the present invention.